DESCRIPTION: This is a revised application seeking four years of funding to study structure-function relationships of the human erythropoietin receptor. The Principal Investigator has cloned the human erythropoietin receptor cDNA using the known murine sequence, and localized the gene to chromosome 19p. The goals of the project are broad, ranging from identification of ligand-binding sites of the external domain, analysis of the signal transducing properties of the cytoplasmic domain, analysis of receptor turnover, and studies of the regulation of the receptor gene in normal and leukemic erythroid cells.The investigator recognizes that similar work is being conducted by several groups using the murine receptor, but he correctly points out that studies on the human receptor are warranted in order to better understand human diseases such as polycythemia vera.